The purpose of this project is to define the humoral and cellular immune responses that relate to immunodiagnosis, immunopathology, and protective immunity of patients with lymphatic filariasis, onchocerciasis, and loiasis. Serodiagnosis of new or prepatent onchocerciasis infections has been made feasible through the use of a purified recombinant onchocercal antigen (OV16). Serologic assays for filarial infection based on IgG4 antibody detection have also been shown to have enhanced specificity, but such antibodies require 6-9 months to develop despite the strong stimulation of chronic helminth infection. Molecular screening has identified recombinant antigens that provide for specific diagnosis of lymphatic filariasis. The nature of the renal abnormalities in lymphatic filariasis has been examined and found to be expressed as hematuria with or without proteinuria. The enhancement of the hematuria during treatment and its resolution after therapy points to immune complex deposition as the underlying mechansism. Populations with bancroftian filariasis or onchocerciasis have been examined to define immunologic parameters that distinguish "naturally immune" from infected individuals. A 43kD protein from infective larvae that may be a protective immunogen for bancroftian filariasis has been cloned and sequenced. Similar studies in onchocerciasis and in another focus of lymphatic filariasis have also been initiated.